Journal:Acta Cryst F:S2053230X19004618

Novel T9 loop interaction of Filamenting Temperature-sensitive mutant Z from Mycobacterium tuberculosis

E. O. Lazo, J. Jakoncic, S. RoyChowdhury, D. Awasthi, I. Ojima ^[1]

Molecular Tour
As of 2017, tuberculosis has infected 1.7 billion people (23% of the world's population) and has caused 10 million deaths. Mycobacterium tuberculosis (Mtb) is quickly evolving, and new strains are classified as multi-drug resistant. Thus, the development and discovery of new drugs to combat Mtb is vital to combat the drug-resistant strains. Filamenting temperature-sensitive mutant Z (FtsZ), an important protein involved in cell-division is key for the survival of Mtb. Here, we have solved the crystal structure of MtbFtsZ that exhibit an inter-subunit that plays a biological role in the GTPase activity of MtbFtsZ and have elucidated a novel conformation, involving the T9 loop and the nucleotide binding pocket that breaks up the GTPase active site. This novel conformation can serve as basis for the development of the novel drugs to combat tuberculosis.

(5v68). Protomers A and C shown in blue, protomer B shown in gray, protomers D and F shown in red, protomer E shown in cyan, GDP are represented by orange spheres, and PO4 by green spheres. . Same color scheme as in previous scene.

Comparison of other MtbFtsZ structures with trimer ABC from 5v68 reveals that protomers A and B superimposed well but the conformation of protomer C is vastly different. . Nucleotide for both is GDP. Color scheme is as follows, 5v68 blue, 4kwe yellow, nucleotides orange spheres, Glu231 green spheres, phosphate red spheres. . The trimer ABC from 5v68 is to a curved MtbFtsZ protofilament (PDB 4kwe). Based on an r.m.s.d. of 1.2Å between protomers AB of 5v68 and protomers CB of 4kwe, protomers A and B from 5v68 are similar with protomers C and B of 4kwe. .

. Color scheme is as follows, 5v68 blue, 2q1y green, nucleotides orange spheres, Glu231 green spheres, phosphate red spheres.

References

1. ↑ Lazo EO, Jakoncic J, RoyChowdhury S, Awasthi D, Ojima I. Novel T9 loop conformation of filamenting temperature-sensitive mutant Z from Mycobacterium tuberculosis. Acta Crystallogr F Struct Biol Commun. 2019 May 1;75(Pt 5):359-367. doi:, 10.1107/S2053230X19004618. Epub 2019 Apr 24. PMID:31045565 doi:http://dx.doi.org/10.1107/S2053230X19004618